Tirzepatide for Weight Loss in Breast Cancer

(FITWISE Trial)

Recruiting at 6 trial locations

Overseen By Coral Omene, MD., PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Rutgers, The State University of New Jersey

Disqualifiers: Stage IV cancer, Type 1 diabetes, Active malignancy, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 104 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This clinical trial aims to evaluate the effectiveness of tirzepatide in achieving a 5% or more body weight reduction in patients undergoing adjuvant treatment for hormone receptor-positive, HER2-negative (HR+/Her2-) breast cancer. The study will also assess the safety and tolerability of tirzepatide, its feasibility based on discontinuation rates, and completion of treatment. Secondary objectives include evaluating 3-year invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS), changes in BMI and body fat distribution, metabolic markers, and circulating tumor DNA (ctDNA).

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What makes the drug Tirzepatide unique for weight loss in breast cancer?

Tirzepatide is unique because it combines two hormone-based actions (GIP and GLP-1 receptor agonists) to help with weight loss, which is not a standard approach in breast cancer treatment. This dual action is different from other treatments that typically target cancer growth pathways. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Tirzepatide for weight loss in breast cancer?

Research shows that Tirzepatide, a drug that helps control blood sugar, also leads to significant weight loss in people with type 2 diabetes. This suggests it might help with weight loss in other conditions, like breast cancer, too. ^{6 7 8 9 10}

Who Is on the Research Team?

Coral Omene, MD, PhD

Principal Investigator

Rutgers Cancer Institute

Are You a Good Fit for This Trial?

This trial is for individuals with early-stage hormone receptor-positive, HER2-negative breast cancer who are undergoing adjuvant treatment and aim to lose at least 5% body weight. Details on specific inclusion or exclusion criteria were not provided.

Inclusion Criteria

I have tumor samples from a biopsy or surgery available.

My breast cancer is hormone receptor-positive and HER2-negative.

I have completed all recommended treatments for breast cancer with the goal of curing it.

Exclusion Criteria

I have a severe stomach emptying issue or take medication that affects my stomach's movement.

My breast cancer is either HER2-positive or triple-negative.

My daily activity is limited due to my health condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tirzepatide for weight loss during adjuvant treatment for HR+/Her2- breast cancer. The dosage starts at 2.5 mg and can be increased to a maximum of 15 mg weekly.

104 weeks

Weekly visits for dose administration

Follow-up

Participants are monitored for safety, effectiveness, and long-term outcomes such as 3-year invasive disease-free survival and distant relapse-free survival.

52 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Tirzepatide

Trial Overview The trial tests Tirzepatide's ability to help patients lose weight during breast cancer treatment. It also looks at the drug's safety, how many people can finish the treatment without stopping, and its impact on survival rates and body composition over three years.

How Is the Trial Designed?

Group I: Tirzepatide Experimental Treatment 1 Intervention

Tirzepatide will be administered subcutaneously in the stomach, upper arm, or thigh, rotating injection sites with each dose. Administer once weekly at any time of day, with or without meals. Start with an initial dosage of 2.5 mg. After 4 weeks, increase to 5 mg weekly. Further increases may be made in 2.5 mg increments after at least 4 weeks on the current dose, aiming for a target of 15 mg (i.e., 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, or 15 mg). Consider treatment tolerability when selecting the maintenance dose. If not tolerated, consider the next lower maintenance dose. Recommended maintenance doses are 5 mg, 10 mg, or 15 mg, with 5 mg as the lowest evaluable dose. The 2.5 mg dose is not a maintenance dose. The maximum allowed dosage is 15 mg once weekly.

Tirzepatide is already approved in United States, European Union, Canada, United Kingdom for the following indications:

Approved in United States as Mounjaro for:

• Type 2 diabetes

Approved in European Union as Mounjaro for:

• Type 2 diabetes

Approved in Canada as Mounjaro for:

• Type 2 diabetes

Approved in United States as Zepbound for:

• Weight loss
• Moderate to severe obstructive sleep apnea

Approved in United Kingdom as Zepbound for:

• Weight loss

Who Is Running the Clinical Trial?

Rutgers, The State University of New Jersey

Lead Sponsor

Trials

471

Recruited

81,700+

Ludwig Institute for Cancer Research

Collaborator

Trials

62

Recruited

1,700+

Published Research Related to This Trial

Tirzepatide, a dual GIP and GLP-1 receptor agonist, showed greater improvements in glucose control and weight loss compared to the GLP-1 receptor agonist dulaglutide in a study involving 316 participants with type 2 diabetes.

The improvements in insulin sensitivity and beta-cell function with tirzepatide were only partially linked to weight loss, indicating that its dual receptor action provides unique mechanisms for better glycemic control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual GIP and GLP-1 Receptor Agonist Tirzepatide Improves Beta-cell Function and Insulin Sensitivity in Type 2 Diabetes. Thomas, MK., Nikooienejad, A., Bray, R., et al.[2022]

Tirzepatide, approved in 2022, is a novel treatment for type 2 diabetes that acts on both GLP-1 and GIP pathways, showing significant efficacy in lowering blood sugar levels and promoting weight loss in various patient groups.

Clinical trials, including the SURPASS and SURMOUNT studies, indicate that tirzepatide has a safety profile similar to traditional GLP-1 receptor agonists, with common gastrointestinal side effects, making it a promising option for patients needing better glycemic and weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide: Clinical review of the "twincretin" injectable. Krauss, Z., Hintz, A., Fisk, R.[2023]

In a systematic review of randomized controlled trials involving 5800 patients, tirzepatide was found to be highly effective for weight loss, with 78.22% achieving at least 5% weight loss and 32.28% achieving at least 15% weight loss.

Tirzepatide demonstrated superior weight loss compared to placebo and semaglutide, with a significant mean weight loss of -12.47 kg at the 5 mg dose, while showing a manageable safety profile with only a slight increase in gastrointestinal adverse events compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of tirzepatide for treatment of overweight or obesity. A systematic review and meta-analysis. Tan, B., Pan, XH., Chew, HSJ., et al.[2023]

Tirzepatide, a once-weekly medication for type 2 diabetes, not only improves blood sugar control but also leads to significant weight loss and positive changes in cardiovascular health, such as reduced blood pressure and improved insulin sensitivity.

The weight loss and metabolic benefits of tirzepatide are linked to its dual action as a GIP and GLP-1 receptor agonist, suggesting that these mechanisms play a crucial role in its effectiveness for managing type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perspectives on weight control in diabetes - Tirzepatide. Várkonyi, TT., Pósa, A., Pávó, N., et al.[2023]

Tirzepatide demonstrated a dose-dependent ability to lower HbA1c levels in adults with type 2 diabetes, with reductions ranging from -17.71 to -22.35 mmol/mol compared to placebo, and was also more effective in reducing body weight than other treatments.

While tirzepatide did not increase the risk of hypoglycaemia compared to placebo and showed lower rates than basal insulin, it was associated with a higher incidence of gastrointestinal side effects, particularly nausea and vomiting, especially at the 15 mg dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of type 2 diabetes with the dual GIP/GLP-1 receptor agonist tirzepatide: a systematic review and meta-analysis. Karagiannis, T., Avgerinos, I., Liakos, A., et al.[2023]

The study established the recommended phase 2 doses (RP2D) for alpelisib (350 mg) and buparlisib (100 mg) when combined with tamoxifen and goserelin in premenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer, showing that both combinations were well-tolerated.

Patients treated with alpelisib experienced a longer progression-free survival of 25.2 months compared to 20.6 months for those on buparlisib, suggesting that alpelisib may be a more effective option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase Ib Study of Alpelisib or Buparlisib Combined with Tamoxifen Plus Goserelin in Premenopausal Women with HR-Positive HER2-Negative Advanced Breast Cancer. Lu, YS., Lee, KS., Chao, TY., et al.[2021]

The maximum tolerated dose (MTD) of buparlisib, an oral PI3K inhibitor, combined with fulvestrant was determined to be 100 mg daily, with a clinical benefit rate of 58.6% in postmenopausal women with metastatic ER(+) breast cancer, indicating promising efficacy.

Common side effects included fatigue, elevated liver enzymes, and rash, but the treatment was manageable, and intermittent dosing reduced toxicity, suggesting a safer administration strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase I Trial of BKM120 (Buparlisib) in Combination with Fulvestrant in Postmenopausal Women with Estrogen Receptor-Positive Metastatic Breast Cancer. Ma, CX., Luo, J., Naughton, M., et al.[2019]

Alpelisib (PIQRAY®) is the first PI3K inhibitor approved for treating hormone receptor-positive metastatic breast cancer with PIK3CA mutations, showing promising clinical results that support its use in overcoming endocrine resistance.

The review highlights the pharmacodynamic and pharmacokinetic properties of alpelisib, along with safety and efficacy data from the Phase III SOLAR-1 trial, which led to its FDA approval, indicating its potential as a tailored treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alpelisib in the treatment of metastatic HR+ breast cancer with PIK3CA mutations. Mavratzas, A., Marmé, F.[2021]

The novel ERβ agonist liquiritigenin (Liq) enhances the effectiveness of temozolomide (TMZ) in treating TMZ-resistant glioma cells by increasing ERβ expression and inhibiting the protective PI3K/AKT/mTOR signaling pathway.

This study suggests that combining ERβ agonists like Liq with TMZ could be a promising strategy to overcome drug resistance in glioma treatment, as the PI3K/AKT/mTOR pathway is often hyperactivated in these tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Estrogen receptor β agonist enhances temozolomide sensitivity of glioma cells by inhibiting PI3K/AKT/mTOR pathway. Liu, X., Wang, L., Chen, J., et al.[2021]

The dual PI3K/mTOR inhibitor NVP-BEZ235 effectively inhibits the growth of various thyroid cancer cell lines, particularly showing the greatest sensitivity in anaplastic thyroid cancer (ATC) cells, without causing toxicity in animal models.

BEZ235 demonstrates synergistic effects when combined with the chemotherapy drug paclitaxel, suggesting a promising treatment strategy for ATC that warrants further clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Utility of a PI3K/mTOR inhibitor (NVP-BEZ235) for thyroid cancer therapy. Lin, SF., Huang, YY., Lin, JD., et al.[2021]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Dual GIP and GLP-1 Receptor Agonist Tirzepatide Improves Beta-cell Function and Insulin Sensitivity in Type 2 Diabetes. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Tirzepatide: Clinical review of the "twincretin" injectable. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of tirzepatide for treatment of overweight or obesity. A systematic review and meta-analysis. [2023]

4. Ireland pubmed.ncbi.nlm.nih.gov

Perspectives on weight control in diabetes - Tirzepatide. [2023]

5. Germany pubmed.ncbi.nlm.nih.gov

Management of type 2 diabetes with the dual GIP/GLP-1 receptor agonist tirzepatide: a systematic review and meta-analysis. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

A Phase Ib Study of Alpelisib or Buparlisib Combined with Tamoxifen Plus Goserelin in Premenopausal Women with HR-Positive HER2-Negative Advanced Breast Cancer. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

A Phase I Trial of BKM120 (Buparlisib) in Combination with Fulvestrant in Postmenopausal Women with Estrogen Receptor-Positive Metastatic Breast Cancer. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Alpelisib in the treatment of metastatic HR+ breast cancer with PIK3CA mutations. [2021]

9. Greece pubmed.ncbi.nlm.nih.gov

Estrogen receptor β agonist enhances temozolomide sensitivity of glioma cells by inhibiting PI3K/AKT/mTOR pathway. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Utility of a PI3K/mTOR inhibitor (NVP-BEZ235) for thyroid cancer therapy. [2021]